Amidoglycosylation Reactions of Glycal Metallanitrenes

糖金属氮烯的酰胺糖基化反应

• 批准号: 7629238
• 负责人: CHRISTIAN M. ROJAS
• 金额: $ 0.94万
• 依托单位: BARNARD COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7629238
• 关键词: Acids; Affect; Alkenes; Amino Sugars; Arts; Aziridines; Biological; Carbamates; Chemistry; Chemistry, Other; Chitinase; Complex; Coupling; Development; Disaccharides; Electrons; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Ethers; Ethyl Ether; Face; Glucal; Goals; Investigation; Iodine; Link; Membrane Glycoproteins; Metals; Methodology; Methods; Modeling; Molecular; Molecular Conformation; Nitrogen; Object Attachment; Organic Chemicals; Organic Chemistry; Outcome; Oxidants; Polymers; Preparation; Process; Range; Reaction; Research; Rhodium; Role playing therapy; Route; Students; System; Technology; Testing; Woman; abstracting; allosamidin; allosamine; amidation; analog; aziridine; base; carboxylate; career; catalyst; chemical synthesis; college; design; enol; forging; glycosylation; improved; inhibitor/antagonist; insight; iodosobenzene; metal complex; method development; nitrene; oxidation; programs; research and development; stereochemistry; sugar

Project Summary/Abstract: The goals of the proposed research are the development, mechanistic description, and application of new methodology for the synthesis of 2-amino sugars, crucial molecular components and precursors in biological systems, including structural polymers, enzyme inhibitors, and cell-surface glycoproteins. The synthetic approach uses glycal 3-carbamates as starting materials and proceeds through a tandem alkene amidation- glycosylation sequence-amidoglycosylation-to introduce nitrogen at C2 of the sugar framework and to establish an anomeric linkage to a nucleophilic reaction partner, the glycosyl acceptor. Iodosobenzene carries out this overall oxidation, in a process best catalyzed by dirhodium(II) carboxylates and apparently involving a rhodium-complexed acyl nitrene intermediate. The amidation step is intramolecular, forging the C2-N bond on the more hindered glycal face, and, ideally, glycosylation should occur stereospecifically, anti to the newly incorporated nitrogen substituent. While certain glycal 3-carbamates react with efficiency and high anomeric stereoselectivity, other substrates with potentially high synthetic value provide substantial amounts of C3-oxidized dihydropyranone byproducts and low stereocontrol in the glycosylation step. Using the mechanistic hypotheses that (1) both amidoglycosylation and C3 oxidation occur via a common metallanitrene intermediate and (2) stereoselective glycosylation requires neighboring-group participation from the C2 nitrogen, probably by way of a glycosyl aziridine, this application outlines how controlling the conformation of the glycal 3-carbamate framework will enable both high chemo- and stereoselectivity in the amidoglycosylation reactions. Other proposed investigations will further illuminate mechanistic details of the reactions, providing crucial information for improving and increasing the utility and scope of amidoglycosylation for the preparation of amino sugars. With input from both the method development and mechanistic study components of the proposed project, this application outlines the completion of a synthesis of the disaccharide portion of the potent chitinase inhibitor allosamidin. Iterative application of the amidoglycosylation technology will enable streamlined preparation of an allosamidin disaccharide module readily amenable for analogue synthesis. To be conducted at Barnard College, an undergraduate liberal arts college for women, the project will provide students with numerous opportunities in organic chemical synthesis, helping to attract and propel them into careers in chemistry and other health-related professions.

项目概要/摘要： 建议研究的目标是开发，机理描述，和新的应用 2-氨基糖、生物学中的关键分子组分和前体的合成方法 系统，包括结构聚合物，酶抑制剂和细胞表面糖蛋白。合成 方法使用甘油3-氨基甲酸酯作为起始材料，并通过串联烯烃酰胺化进行， 糖基化序列-酰胺基糖基化-在糖框架的C2处引入氮， 建立与亲核反应配偶体（糖基受体）的异头键。碘酰苯携带 在最好由二铑（II）羧酸盐催化的过程中， 铑络合的酰基氮烯中间体。酰胺化步骤是分子内的，在分子上锻造C2-N键。 糖基表面受阻越多，理想地，糖基化应该立体特异性地发生，与新的糖基化相反。 引入的氮取代基。而某些糖基3-氨基甲酸酯反应效率高， 尽管存在立体选择性，但具有潜在高合成价值的其它底物提供了大量的 C3-氧化二氢吡喃酮副产物和糖基化步骤中的低立体控制。使用 机理假说：（1）酰胺基糖基化和C3氧化均通过共同的金属苯胺氮发生 中间体和（2）立体选择性糖基化需要相邻基团的参与，从C2 氮，可能通过糖基氮丙啶的方式，本申请概述了如何控制 糖基3-氨基甲酸酯骨架将使得在酰胺基糖基化中具有高化学选择性和立体选择性 反应.其他拟议的调查将进一步阐明反应的机理细节，提供 改善和增加酰胺基糖基化制备的效用和范围的重要信息 氨基糖随着输入的方法开发和机制研究的组成部分， 建议的项目，本申请概述了合成的二糖部分的完成， 有效的几丁质酶抑制剂阿洛酰胺。酰胺基糖基化技术的反复应用将使 一种易于用于类似物合成的别氨基菌素二糖模块的流线型制备。到 该项目将在巴纳德学院（Barnard College）进行，巴纳德学院是一所女子文科大学，该项目将提供 学生在有机化学合成的众多机会，帮助吸引和推动他们进入 从事化学和其他与健康相关的职业。

项目成果

Dihydropyranone formation by ipso C-H activation in a glucal 3-carbamate-derived rhodium acyl nitrenoid.

在葡萄糖 3-氨基甲酸酯衍生的铑酰基氮烯化合物中通过 ipso C-H 活化形成二氢吡喃酮。

• DOI: 10.1021/jo101599q
• 发表时间: 2011
• 期刊: The Journal of organic chemistry
• 作者: Hurlocker,Brisa;Abascal,NadiaC;Repka,LindsayM;Santizo-Deleon,Elsy;Smenton,AbigailL;Baranov,Victoria;Gupta,Ritu;Bernard,SarahE;Chowdhury,Shenjuti;Rojas,ChristianM
• 通讯作者: Rojas,ChristianM

Protecting group and solvent control of stereo- and chemoselectivity in glucal 3-carbamate amidoglycosylation.

葡萄糖3-氨基甲酸酯酰胺糖基化中立体选择性和化学选择性的保护基团和溶剂控制。

• DOI: 10.1021/ol900126q
• 发表时间: 2009
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Gupta,Ritu;Sogi,KimberlyM;Bernard,SarahE;Decatur,JohnD;Rojas,ChristianM
• 通讯作者: Rojas,ChristianM